MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma
- Conditions
- Unresectable Pleural Mesothelioma
- Interventions
- Registration Number
- NCT06097728
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of Volrustomig (MEDI5752) + Carboplatin + Pemetrexed vs the investigator's choice of platinum + Pemetrexed or Nivolumab + Ipilimumab in participants with unresectable pleural mesothelioma.
- Detailed Description
Adult patients with histologically proven diagnosis of pleural mesothelioma with advanced unresectable disease are eligible to be enrolled. Patients will be randomized 1:1 to receive Volrustomig (MEDI5752) + Carboplatin + Pemetrexed or the investigator's choice of platinum+Pemetrexed or Nivolumab+Ipilimumab, based on their histology.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 600
- Participant must be ≥ 18 years at the time of screening
- Histologically proven diagnosis of pleural mesothelioma with known histology (epithelioid vs. non-epithelioid)
- Advanced unresectable disease that cannot be treated with curative surgery (with or without chemotherapy)
- WHO/ECOG performance status of 0 or 1 with no deterioration (that is, ECOG PS>1) over the previous 2 weeks prior to day of first dosing
- Has measurable disease per modified RECIST1.1
- Has adequate bone marrow reserve and organ function at baseline
Key
- As judged by the investigator, any condition that would interfere with evaluation of the investigational product or interpretation of participant safety or study results.
- Active or prior documented autoimmune or inflammatory disorders
- History of another primary malignancy with exceptions.
- Uncontrolled intercurrent illness
- Tuberculosis, hepatitis B (HBV) or hepatitis C (HCV), human immunodeficiency virus (HIV) infection that is not well controlled
- Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment
- Untreated or progressive CNS metastatic disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Volrustomig + Carboplatin + pemetrexed Volrustomig Volrustomig in combination with carboplatin plus pemetrexed Volrustomig + Carboplatin + pemetrexed Pemetrexed Volrustomig in combination with carboplatin plus pemetrexed Investigator's choice of standard care Ipilimumab The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology. Volrustomig + Carboplatin + pemetrexed Carboplatin Volrustomig in combination with carboplatin plus pemetrexed Investigator's choice of standard care Pemetrexed The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology. Investigator's choice of standard care Carboplatin The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology. Investigator's choice of standard care Cisplatin The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology. Investigator's choice of standard care Nivolumab The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) in experimental arm relative to comparator arm up to approximately 52 months OS is defined as the time from randomization until the date of death due to any cause.
- Secondary Outcome Measures
Name Time Method Landmark OS 12, 18, 24, 36 months Landmarks of OS12, OS18, OS24, and OS36.
Landmark PFS 6, 12, 18, 24 months Landmarks of PFS6, PFS12, PFS18, and PFS24
PFS2 up to approximately 52 months PFS2 defined as the time from randomization to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.
Maximum plasma concentration of the drug (Cmax) Up to approximately 52 months The concentration of MEDI5752 in serum will be determined (Cmax will be derived).
Patient-reported HRQoL (Health-related Quality of Life) using EORTC QLQ-C30 HRQoL subscale (IL305 Q7-8) Up to approximately 52 months Change from baseline in functioning will be assessed by the following measure:
HRQoL: EORTC (European Organisation For Research And Treatment Of Cancer) QLQ (Quality of Life Questionnaire) -C30 HRQoL subscale (IL305 Q7-8) (Item Library 305). The questions are from a scale of 1 (very poor) to 7 (excellent). The higher the score the higher the HRQoL.Overall Survival (OS) up to approximately 52 months OS is defined as the time from randomization until the date of death due to any cause.
Duration of Response (DoR) up to approximately 52 months DoR defined as the time from the date of first documented response until date of documented progression per mRECIST 1.1 and/or RECIST 1.1 as assessed by the investigator at local site or death due to any cause.
Patient-reported physical functioning up to approximately 52 months. TTD in physical functioning as measured by PROMIS (Patient Reported Outcomes Measurement Information System) Physical Function Short Form 8c. There are 8 questions each from a scale of 1 (unable to do) to a scale of 5 (With a little difficulty). The higher the scores the better the patient-reported physical functioning is.
Disease-related symptoms using PRO-CTCAE (Q1, 5, 6, 9) Up to approximately 52 months Change from baseline in disease-related symptoms as measured by individual symptom items from the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) (Q1, 5, 6, 9). PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present). The higher the score the higher the disease-related symptoms.
Patient-reported role functioning using EORTC QLQ-C30 RF subscale (IL305 Q2 3) up to approximately 52 months Change from baseline in functioning will be assessed by the following measure:
Role functioning: EORTC (European Organisation For Research And Treatment Of Cancer) QLQ (Quality of Life Questionnaire) -C30 RF (Role Functioning) subscale (IL305 Q2 3) (Item Library 305). The questions are from a scale of 1 (not at all) to 4 (very much). The lower the score the higher the patient-reported role functioning is.Immunogenicity of volrustomig up to approximately 52 months Incidence of Anti-Drug Antibodies against volrustomig.
Overall Response Rate (ORR) up to approximately 52 months Proportion of participants who have a confirmed Complete Response or confirmed Partial Response, as determined by the investigator at local site per mRECIST 1.1 and/or RECIST 1.1.
The time taken to reach the maximum concentration (Tmax) Up to approximately 52 months The concentration of MEDI5752 in serum will be determined (Tmax will be derived).
Progression Free Survival (PFS) up to approximately 52 months PFS is defined as the time from randomization until progression per mRECIST 1.1 and/or RECIST 1.1 as assessed by the investigator at local site, or death due to any cause.
Disease-related symptoms using EORTC IL305 (Q1) Up to approximately 52 months. Change from baseline in disease-related symptoms as measured by individual symptom items from the EORTC (European Organisation For Research And Treatment Of Cancer) IL305 (Item Library 305) (Q1). It is scored from a 1 (not at all) to a 4 (very much). The higher the score the higher the disease-related symptoms.
Area under the curve (AUC) Up to approximately 52 months The concentration of MEDI5752 in serum will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.
Incidence of Adverse Events (AEs) AEs graded by CTCAE version 5.0 Up to approximately 52 months Incidence of Adverse Events (AEs) AEs graded by CTCAE (Common Terminology Criteria for Adverse Events) version 5.0. Grade refers to the severity of the AE. The CTCAE displays grade 1 (mild) through 5 (death related to AE). Grade 2 (moderate), Grade 3 (Severe) and Grade 4 (Life-threatening consequences).
Trial Locations
- Locations (1)
Research Site
🇬🇧Taunton, United Kingdom